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Updated: Nov 3, 2025
Fracture Apparatus Design and Protocol Optimization for Closed-stabilized Fractures in Rodents
Published on: August 14, 2018
The TrkB agonist, 7,8-dihydroxyflavone, impairs fracture healing in mice
Maddison R Johnstone1, Rhys D Brady2, Jarrod E Church1
1Department of Physiology, Anatomy and Microbiology, School of Life Sciences, La Trobe University, Melbourne, Australia.
Objectives:
To study the effects of the selective TrkB agonist, 7,8-dihydroxyflavone (7,8-DHF), on fracture healing in mice and on an osteoprogenitor cell line, Kusa4b10, in vitro.
Methods:
Mice received unilateral closed mid-shaft tibial fractures and treated for two weeks with vehicle or 5 mg/kg/day DHF and euthanised at 28 days post-fracture. Calluses were analysed by micro-computed tomography (μCT) and three-point bending biomechanical test. Kusa4b10 cells were cultured with 50nM of 7,8-DHF or vehicle for 3-, 7-, 14-days for RT-PCR, and 21 days for mineralization.
Results:
μCT found 7,8-DHF calluses had decreased tissue volume (p=0.042), mean polar moment of inertia (p = 0.004), and mean cross-sectional area (p=0.042) compared to controls. At 28 days biomechanical analyses showed 7,8-DHF treatment decreased peak force (p=0.011) and stiffness per unit area (p=0.012). 7,8-DHF treatment did not change Kusa4b10 gene expression of Runx2 and alkaline phosphatase at all time points, nor mineralization.
Conclusions:
7,8-DHF treatment had a negative impact on fracture healing at 28 days post-fracture via an unknown mechanism. 7,8-DHF may have had a central role in impairing fracture healing.
Insights
The selective TrkB agonist, 7,8-dihydroxyflavone (7,8-DHF), negatively impacted fracture healing in mice. This compound impaired callus formation and biomechanical strength, suggesting a detrimental role in bone repair.
Area of Science:
- Biomedical Science
- Orthopedics
- Pharmacology
Background:
- The TrkB receptor signaling pathway plays a crucial role in neuronal development and function.
- Investigating the role of TrkB agonists in non-neuronal tissues, such as bone, is an emerging area of research.
- Understanding the impact of 7,8-dihydroxyflavone (7,8-DHF) on bone healing could reveal new therapeutic targets.
Purpose of the Study:
- To evaluate the effects of the selective TrkB agonist, 7,8-dihydroxyflavone (7,8-DHF), on fracture healing in a mouse model.
- To assess the impact of 7,8-DHF on osteoprogenitor cells in vitro.
Main Methods:
- Unilateral closed mid-shaft tibial fractures were induced in mice, followed by two weeks of treatment with vehicle or 7,8-DHF (5 mg/kg/day).
- Fracture calluses were analyzed at 28 days post-fracture using micro-computed tomography (μCT) and biomechanical testing.
- Osteoprogenitor Kusa4b10 cells were treated with 7,8-DHF in vitro for gene expression and mineralization assays.
Main Results:
- Micro-CT analysis revealed decreased callus tissue volume, mean polar moment of inertia, and mean cross-sectional area in 7,8-DHF treated mice.
- Biomechanical testing showed reduced peak force and stiffness per unit area in the 7,8-DHF group at 28 days.
- In vitro studies indicated that 7,8-DHF did not alter gene expression of Runx2 and alkaline phosphatase or mineralization in Kusa4b10 cells.
Conclusions:
- 7,8-dihydroxyflavone (7,8-DHF) treatment demonstrated a negative impact on fracture healing in mice at 28 days post-fracture.
- The mechanism by which 7,8-DHF impairs fracture healing remains unknown.
- Further investigation is warranted to elucidate the role of 7,8-DHF in bone repair processes.
